It is the aim of this project to develop non-invasive methods for the study of drug and steroid biotransformation in children. We will study children that have diseases or are taking medications that are known to alter the drug and steroid metabolizing capacity in adults. Several disease states, including liver disease, endocrine disorders and an increasing number of drugs have been shown to alter the adult's capacity to metabolize drug and steroid hormones: 1. The rate of metabolism of a model drug (antipyrine) will be studied in two biological fluids, blood and saliva. Antipyrine will serve as an indicator of the rate of metabolism of a drug principally metabolized by the mixed function oxidase system in the liver microsomes. 2. Simultaneously, the urinary excretion of 6 beta-hydroxycortisol, the most important unconjugated metabolite of cortisol, will be measured by RIA and 6 beta-hydroxycortisol excretion may also serve as a useful, non-invasive indicator for the study of induction and inhibition of drug metabolism by drugs and hormones. In the coming year we will conclude our clinical investigation comparing non-invasive 6 beta OHF/FF measurements with measurements of antipyrine clearance in blood and saliva of patients on anticonvulsants and in lead poisoned children. If 6 beta OHF/FF shows a good correlation, with antipyrine metabolism, in individual subjects, this would provide a rational basis for the broader use of 6 beta OHF/FF measurements when studying effects of anticonvulsants and possibly of other drugs on microsomal hydroxylation.